US 11,746,139 B2
IL-7Rαγc binding compounds
William J. Dower, Menlo Park, CA (US); Michael C. Needels, Menlo Park, CA (US); Ronald W. Barrett, Menlo Park, CA (US); Alice V. Bakker, Menlo Park, CA (US); and Steven E. Cwirla, Menlo Park, CA (US)
Assigned to MEDIKINE, INC., Menlo Park, CA (US)
Filed by MEDIKINE, INC., Menlo Park, CA (US)
Filed on Feb. 3, 2021, as Appl. No. 17/166,462.
Claims priority of provisional application 63/041,158, filed on Jun. 19, 2020.
Claims priority of provisional application 62/969,432, filed on Feb. 3, 2020.
Prior Publication US 2021/0253670 A1, Aug. 19, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/715 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/7155 (2013.01) [A61K 38/00 (2013.01); C07K 2319/00 (2013.01); C07K 2319/30 (2013.01)] 37 Claims
 
1. An IL-7Rαγc ligand comprising:
(a) an IL-7Rα ligand, wherein,
the IL-7Rα ligand binds to the human IL-7Rα subunit with an IC50 of less than 100 μM; and
the IL-7Rα ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 7, 15, 40, 60, 82, 87, 103, 115, 121, 177, 193, 210, 335, 381, 384, 402, 407, 582, and 655:
 
 SEQ ID NO: 7
 
 T C Q H Q D L Q G L L A C I
 
 
 
 SEQ ID NO: 15
 
 D W L C R P G P G L L V C Q W F
 
 
 
 SEQ ID NO: 40
 
 L Y C A E L H G F R V C R L
 
 
 
 SEQ ID NO: 60
 
 N I A C M R F P G G Y V C R N Y
 
 
 
 SEQ ID NO: 82
 
 V C R T T R L D N W W G C R
 
 
 
 SEQ ID NO: 87
 
 H C R L Q K P G F H R S S C
 
 
 
 SEQ ID NO: 103
 
 Y W A C S S G M N L C R W N
 
 
 
 SEQ ID NO: 115
 
 D C Y H W D L E S L L A C L
 
 
 
 SEQ ID NO: 121
 
 H C L H W D I E T L M S C V Y G N F E E
 
 
 
 SEQ ID NO: 177
 
 Y C M H W D L E S L L W C V H R K E L E
 
 
 
 SEQ ID NO: 193
 
 D R M V T G I P W C L L D P G S I Q C A W L
 
 
 
 SEQ ID NO: 210
 
 I P W C T L D P G S V Q C D Y L L K S A K Q
 
 
 
 SEQ ID NO: 335
 
 V P W C V L D P G S I Q C E Y L Q R L H R Q
 
 
 
 SEQ ID NO: 381
 
 R I E C A E L P G G F T C R L R
 
 
 
 SEQ ID NO: 384
 
 R Y E C A D L P G G L H C E F R
 
 
 
 SEQ ID NO: 402
 
 Q C V H W D L D T L F G C I R E Q L E L
 
 
 
 SEQ ID NO: 407
 
 V H R I P W C T L D P G G L Q C A W L R Q M
 
 
 
 SEQ ID NO: 582
 
 G G R S C L W Q P G A L H C T W W A E E E P V
 
 
 
 SEQ ID NO: 655
 
 G W G I P W C T L D P G S L Q C A W L G K H
(b) an Rγc ligand, wherein,
the Rγc ligand binds to the human Rγc subunit with an IC50 of less than 100 μM; and
the Rγc ligand comprises an amino acid sequence selected from any one of SEQ ID NOS: 950 to 1028:
SEQ ID NO: 950
I E C D T S Y G V Y I C W Q
 
SEQ ID NO: 951
I E C E E W R G V E L C W Q
 
SEQ ID NO: 952
P E G R E V V V C R D W Y G V E L C W Q
 
SEQ ID NO: 953
I W G R T V V E C Q D W E G V E L C W Q
 
SEQ ID NO: 954
L A L R K E V V C Q E Y Y G V E L C W I
 
SEQ ID NO: 955
H E A R E V V V C Q D W Y G V E L C W Q
 
SEQ ID NO: 956
M V N R E V V V C E D W Y G V E L C W Q
 
SEQ ID NO: 957
T A N Q T V V E C Q V W G G V E L C W Q
 
SEQ ID NO: 958
V E C Q E W G G V E L C W C
 
SEQ ID NO: 959
D V E C V D W G G V E L C W H
 
SEQ ID NO: 960
I V C E E W R G V E L C W L
 
SEQ ID NO: 961
D F E R S Y V V C Q D W D G V E L C W I
 
SEQ ID NO: 962
A H S R Q E V V C E E W Y G V E L C W I
 
SEQ ID NO: 963
S A P E R W V E C E D W Q G V E L C W V
 
SEQ ID NO: 964
Y S R E L Y V Q C E D W E G V E L C W I
 
SEQ ID NO: 965
V V C Q D W E G V E L C W Q
 
SEQ ID NO: 966
D V V C Q N W E G V D L C W H
 
SEQ ID NO: 967
S A G R Q E V V C Q D W N G V E L C W I
 
SEQ ID NO: 968
G Q G R E V V V C H D W Y G V E L C W Q
 
SEQ ID NO: 969
D W R R S V V E C Q D W Y G V E L C W Q
 
SEQ ID NO: 970
D V V C Q N W D G V D L C W H
 
SEQ ID NO: 971
T L G R T V V E C Q D W G G V E L C W Q
 
SEQ ID NO: 972
R L L N S V V E C L D W E G V E L C W Q
 
SEQ ID NO: 973
I V C E D W R G V E L C W I
 
SEQ ID NO: 974
V V C Q E W E G V E L C W C
 
SEQ ID NO: 975
G D R P K E V V C E D W K G V E L C W I
 
SEQ ID NO: 976
E R P R S F I E C Q E W E G V E L C W L
 
SEQ ID NO: 977
E G S T T T I E C E E W A G V E L C W L
 
SEQ ID NO: 978
A N Q N T V V E C Q D W H G V E L C W Q
 
SEQ ID NO: 979
R S D D E V V V C Q E W E G V E L C W Q
 
SEQ ID NO: 980
I E C E E W A G V E L C W L
 
SEQ ID NO: 981
T W N M S E L E C Q D W N G V E I C W H
 
SEQ ID NO: 982
G N D D S Y I V C E E W K G V E L C W I
 
SEQ ID NO: 983
F A H H G V V E C Q E W Y G V E L C W Q
 
SEQ ID NO: 984
L N R S V W I E C E E Y E G V E L C W L
 
SEQ ID NO: 985
W S K K A E V V C E E W G G V E F C W I
 
SEQ ID NO: 986
R S N Q T V V E C Q D W E G V E L C W Q
 
SEQ ID NO: 987
V V C Q E W E G V E L C W Y A G E C M Q
 
SEQ ID NO: 988
I L C Q E F E G V E L C W L E E S L A E
 
SEQ ID NO: 989
K S Q V E C Q D W E G V E L C W V V S E
 
SEQ ID NO: 990
K I T V E C Q D W D G V E L C W P T W I
 
SEQ ID NO: 991
R P Q I E C Q E W Q G V E L C W T R E E
 
SEQ ID NO: 992
V S C Q E W D G V E L C W V D G D L A A
 
SEQ ID NO: 993
I M C Q E W D G V E L C W L E R D K A N
 
SEQ ID NO: 994
G L E I A C E D W Y G V E L C W L R R A
 
SEQ ID NO: 995
G Y G V L C Q E W Q G V E L C W P V Q R E A G V
 
SEQ ID NO: 996
P Y G V V C Q D W A G V E L C W V E N R
 
SEQ ID NO: 997
K L T V E C Q D W D G V E L C W V G V E
 
SEQ ID NO: 998
I N C Q T W N G V E L C W V D E G L Y Q
 
SEQ ID NO: 999
V V C Q E W E G V E L C W V E P P L L P
 
SEQ ID NO: 1000
R V Q V E C E D W N G V E L C W P V R V
 
SEQ ID NO: 1001
D R Q V V C E E W D G V E L C W I E E S
 
SEQ ID NO: 1002
K T T V A C Q D W G G V E L C W V E R V
 
SEQ ID NO: 1003
R P E V V C Q E W E G V E L C W I S P L
 
SEQ ID NO: 1004
R L G V E C Q E W E G V D L C W I S A F
 
SEQ ID NO: 1005
K P V V V C E E W Q G V E L C W L E I Q
 
SEQ ID NO: 1006
V V C E V F Q G V E L C W C E N E E F T
 
SEQ ID NO: 1007
T D E V S C Q E W E G V E L C W I E R Q
 
SEQ ID NO: 1008
P V E V R C Q E W E G V E L C W V V G I
 
SEQ ID NO: 1009
G P E V V C E E F N R V E L C W V E Y N
 
SEQ ID NO: 1010
K Y I V E C Q E W G G V E L C W P E M V
 
SEQ ID NO: 1011
V T C Q E Y E G V E L C W T V G C A Y S
 
SEQ ID NO: 1012
V V C Q E W E G V E L C W Q T G P G A H A
 
SEQ ID NO: 1013
I V C E E Y N G V E L C W V E T S V K P
 
SEQ ID NO: 1014
E Q Q V V C Q E W N G V E L C W I E A G
 
SEQ ID NO: 1015
Q L G V E C Q N W R G V E L C W V S E I
 
SEQ ID NO: 1016
T A E V V C Q E W D G V E L C W I E V L
 
SEQ ID NO: 1017
S P S I V C E E W A G V E L C W V D Y S
 
SEQ ID NO: 1018
A V C Q D W Y G V E L C W C M Q D I L D
 
SEQ ID NO: 1019
V E C E E W G G V E L C W L A D E V M W
 
SEQ ID NO: 1020
H S T V I C Q D W D G V E L C W I E N D
 
SEQ ID NO: 1021
K K I V V C Q D W G G V E L C W T E D D
 
SEQ ID NO: 1022
S V E V V C E E W H G V E L C W P V F I
 
SEQ ID NO: 1023
R W A V S C Q D W Q G I E L C W P E W D
 
SEQ ID NO: 1024
R T G V E C Q D W H G V E L C W P V W E
 
SEQ ID NO: 1025
G Y G V V C E D F R G V E L C W L E R K
 
SEQ ID NO: 1026
R T E V E C E D W E G V E L C W L
 
SEQ ID NO: 1027
I L C E E W Q G V E L C W L E G G G S
 
SEQ ID NO: 1028
V G I E C E E W A G V E L C W L
and,
(c) a linker bonding the IL-7Rα ligand to the Rγc ligand.